Thienylalkyl esters of 3-sulphamyl-4-chlorobenzoic acid



United States Patent 3,162,651 THEENYLALKYL ESTERS 0F 3-SULPHAMYL-4-CHLQRGBENZUIC ACID Ernst .lnclrer, Binningen, Basel-Land, and Adolf J.Lindenrnann, Basel, Switzerland, assignors, by mesne assignments, toFidelity Union Trust ompany, executive trustee under Sandoz Trust of May4, 1955 No Drawing. Original application May 8, 1961, Ser. No. 108,308,new Patent No. 3,119,843, dated Jan. 28, 1964. Divided and thisapplication Apr. 30, 1962, Ser. No. 191,268

2 Claims. (Cl. 260332.2)

The present application is a division of our copending applicationSerial No. 108,308, filed May 8, 1961 and now US. Patent No. 3,119,843,granted January 28, 1964.

The present invention relates to new sulphonamides having the structuralFormula I,

llialogen ]OO-AB I wherein A represents methylene and ethylene and B isselected from the group consisting of nitrogen, oxygen and can alsorepresent a sulphur-containing heterocyclic group linked with one of itscarbon atoms to the radical A, their acid addition salts andpharmaceutical compositions containing, in addition to an inert carrier,a compound I and/ or an acid addition salt thereof.

The sulphonamides of this invention and their acid addition salts can beprepared by reacting a compound of the general Formula II,

wherein A and B have the above significance, with a 3-sulphamyl-4-halogenobenzoyl chloride, and when an acid addition salt isrequired, salifying with an organic or inorganic acid.

Suitable meanings for the radical B are, for example, a 2- or 3-furyl ortetrahydrofuryl group, a 2-, 3- or 4- pyridyl 0r -piperidyl group, a 2-,3- or 4-tetrahydropyranyl group, a 2-, 3- or 4-quinolyl group or a 2- or3-thienyl group.

The preparation of the new sulphonamides can be carried out as follows:a suspension of 3-sulphamyl-4-ch1orobenzoyl chloride is mixed with acompound II until complete dissolution has taken place. The excess ofthe compound II is removed by evaporation in a vacuum. The resultingoily residue is then rubbed to crystallize out the required ester whichis then purified.

The compounds of the invention, which are at room temperature solidcrystalline compounds, have interesting pharmacodynamic propertiesand/or may be used as intermediate compounds for the production ofpharmaceuticals. The exemplified compounds show, depending upon thenature of the radical A and B in Formula I, diuretic, sodium uretic andchloride uretic properties. In tests with dogs, they have been found tobe effective on peroral administration; for example3-sulphamyl-4-chlorobenzoic acid-tetrahydrofurfuryl ester has been foundto be a particularly quick acting salidiureticum when administered todogs perorally. 0.5 mg./kg. given to dogs perorally has more thandoubled excretion of electrolyte after 2 hours.

The compounds can be administered in therapeutic dosages in conventionalvehicles as in the form of a tablet as these compounds are effectiveupon oral administration as well as upon injection.

Examples of suitable acids for salifying the compounds I are as follows:hydrochloric, hydrooromic, sulphuric, oxalic, tartaric, acetic,hexahydrobenzoic, methanesulphonic and fumaric acid.

The preparation of these compounds is more fully described in thefollowing example. It is to be understood, however, that th example isillustrative of the compounds embraced by this invention and are not tobe construed as limiting the invention to the particular compoundsspecifically described. All temperatures are stated in degreesCentigrade.

EXAMPLE 1 3-Sulphamyl-4-Chl0robenzoic Acid Thienyl-(2)- Methyl Ester 5.1g. of 3-sulphamyl-4-chlorobenzoyl chloride are added portionwise to asolution of 2.3 g. of thiophene-Z- carbinol and 2.0 g. of triethylaminein 30 cc. of benzene While being stirred. An oil begins to separate fromthe reaction mixture. Stirring of the mixture is continued at 20-25 foranother 60 hours, followed by evaporation in a vacuum until dry. Theoily evaporation residue is divided between 300 cc. of acetic acid ethylester and 300 cc. of water, the two phases being separated and theacetic acid ethyl ester solution dried over magnesium sulphate. Afterthe solvent has been distilled off in a vacuum the oily residue ischromatographed on alumina, the 3- sulphamyl-4-chlorobenzoic acidthienyl-(2)-methyl ester being eluted with a solvent mixture ofchloroform and methanol (9:1). After recrystalization from methanol thesulphonamide derivative melts at 133-134".

We claim:

1. A compound of formula llialogen References (Zited in the file of thispatent UNITED STATES PATENTS Dazzi Apr. 1, 1952 Wilcox et a1 Apr. 23,1957

2. 3-SULPHAMYL-4-CHLOROBENZOIC ACID THIENYL-(2'')-METHYL ESTER.